Health Sciences North

Background: Lemierre’s syndrome (LS), previously termed the “forgotten disease” after the introduction of modern antibiotics, is a rare and potentially fatal infection of the neck resulting in septic thrombophlebitis of the internal jugular and other neck veins. In recent years, there has been an increased resurgence of this disease, or at least in its detection, and it remains an important diagnosis with life-threatening potential to consider when presenting with multifocal cavitary pneumonia. Fusobacterium necrophorum, an obligate anaerobic Gram-negative bacterium, is the most isolated culprit organism involved in this condition; however, it is often fastidious and difficult to culture. The use of 16s rRNA gene sequencing can aid in this diagnosis when uncertainty exists. Methods: This case report describes an otherwise healthy 17-year-old male with a history of regular vaping presenting with upper respiratory infectious symptoms who was ultimately diagnosed with multifocal necrotizing pneumonia. In this case, there was initial diagnostic uncertainty as traditional microbiologic culture mechanisms failed to identify a causative organism for tailored antimicrobial treatment. This was despite direct empyema fluid analysis and pulmonary-bronchial biopsy. Novel gene sequencing was performed using 16s rRNA typing, a promising new way to identify a catalog of host organisms, detecting F. necrophorum. This diagnosis prompted further diagnostic imaging of the neck, confirming a small internal jugular clot and diagnosis of LS. Results: This case highlights the need for suspicion of LS in patients presenting with multifocal pneumonia. Furthermore, it re-iterates the idea of culture-negative infections, whereby fastidious organisms or tissue samples do not readily provide a diagnosis. Lastly, it further introduces hypotheses regarding the use of vaping as a possible associated factor for significant infection and lung injury. Conclusions: The use of 16s rRNA sequencing for the detection of fastidious, opportunistic organisms is another tool for physicians to ensure additional diagnostic clarity and appropriate treatment.

Background: Acute coronary syndrome (ACS) is a "can't miss" diagnosis. The gold-standard workup for this requires serial troponin biomarker evaluation over a period of hours. Traditionally, many of these patients required telemetry while being evaluated in this fashion; however, the high-quality literature suggests that low-risk patients do not require ongoing continuous cardiac monitoring. Locally, it was found that over 70% of patients presenting with low-risk chest pain to our high-volume urgent care were transferred to the main hospital for an ACS rule-out work-up via emergency medical services (EMS). We felt this intersection of patient care and medical services could be streamlined to reduce critical resource utilization. Objective: The aim of this study is to reduce the usage of EMS utilization for transport of low-risk chest-pain patients from the urgent care to the main hospital by 25% over a 3-month period. Methods: This study was conducted as an uncontrolled before-after interrupted time series design. A comprehensive data drilldown was performed through a chart review and structured clinical-practice evaluation. This led to a multi-factorial quality improvement initiative centered around the creation of an evidence-based safe-for-self-transport tool and physician education. The primary outcome measure was the proportion of patients transported via EMS with the main balancing measures being the proportion of self-transported patients admitted to the hospital and the time to troponin blood-draw in self-transported patients. Results: The education and the newly developed transport tool resulted in a sustained shift below the previous baseline system mean control limit, indicating a significant reduction in EMS usage for patient transport. The overall reduction in usage was 30%. No change in balancing (safety) measures was identified post-implementation. Conclusions: EMS remains a finite resource within many Canadian health regions. The results of this study show that by focusing on a cardinal emergency-department presentation like chest pain, adapting evidence-based practice through quality-improvement methodologies can result in a significant sustained reduction in EMS utilization.

Oral wound healing is a robust process; however, complications from surgery, systemic diseases, and aging can impair healing. While some treatments exist, regenerative therapies to promote mucosal wound healing remain limited. In recent years, there has been a significant rise in FDA-approved cell-based therapies; however, extracellular vesicles represent an emerging cell-free alternative that may mitigate risks associated with cellular therapies, including tumorigenesis and immunogenicity. These lipid-encapsulated nanovesicles can deliver therapeutic cargo, such as proteins, lipids, nucleic acids, or drugs, to the wound site. Extracellular vesicles can be derived from mesenchymal stromal cells, immune cells, bodily fluids, or bacteria, and engineered through genetic modification, preconditioning, or direct cargo loading to enhance therapeutic potency. Furthermore, advanced delivery platforms, including hydrogels, microneedles, and aerosols, allow for sustained and localized EV delivery to the oral wound site. This review examines differences between cutaneous and oral wound healing; factors that impair oral repair; extracellular vesicle sources and engineering strategies; and delivery strategies for developing EV-based therapeutics for oral wound healing.

Most clinical cancer therapy trials do not specifically consider the effect of patient age on treatment outcomes, and many even exclude older individuals. This is despite the fact that solid cancers are age-associated diseases and that there are many shared hallmarks between biological ageing and cancer. Thus, there is an increasing awareness of the serious gaps remaining in our knowledge of how older adults respond to cancer treatments, particularly immunotherapies. Emerging evidence suggests that it is not only the physiological and immunological changes associated with chronological ageing that impacts cancer treatment, but also those heterogeneous differences that impact treatment outcomes, such as frailty, comorbidities, and more generally, biological ageing. Importantly, it remains unclear which of these factors are negative or positive contributors, as has been illuminated by recent evidence pertaining to the incidence and severity of immune-related adverse events and survival. Much of our information on older patients in this context is essentially anecdotal, mostly deriving from the treatment of older adults in real-world practice or clinical trials that happened to include some older patients. Given the lack of comprehensive articles on the heterogeneity of ageing as a core determinant of cancer treatment outcomes, we briefly consider the state of the art of cancer research and treatment in the older patient, with an emphasis on immunotherapy and geriatric oncology.

Previous research identified high levels of burnout in the Canadian public health workforce during the COVID-19 pandemic. This study presents the prevalence of burnout, associated participant demographic and workplace characteristics, and associated secondary outcomes among Canadian public health physicians and residents one year after the end of the COVID-19 pandemic. Data were collected using an online survey distributed through Canadian public health associations and professional networks between April and May 2024. Validated tools were used to measure burnout (Oldenburg Burnout Inventory (OLBI)), screen for anxiety (GAD-2) and depression (PHQ-2), and professional fulfillment (Stanford Professional Fulfillment Index). Additional binary (yes/no) questions were asked on workplace safety topics (e.g., threats, assaults, being bullied) and professional plans. Fisher’s exact test and logistic regressions were used to model the association between burnout and sequelae of burnout, including symptoms of depression and anxiety, and professional fulfillment. Among 118 physicians who completed the OLBI, the prevalence of burnout was 63.6%. Additionally, 41.2% of physicians reported being threatened, assaulted or bullied during the pandemic. Physicians who screened positive for anxiety (19.3%) and depression (7.6%) had higher odds of burnout (OR 4.79, 95% CI 1.29-26.90, p = 0.01 and OR 2.10, 95% CI 0.38-21.65, p = 0.48, respectively). Moreover, physicians who had low levels of professional fulfillment (84.9%) also had higher odds of burnout (OR 12.5, 95% CI 3.21-72.76, p < 0.001). The prevalence of burnout among Canadian public health physicians and residents remains high post-pandemic and was associated with symptoms of depression, anxiety and low professional fulfillment. By implementing interventions to prevent and mitigate burnout, and promote recovery, the public health system will be better positioned to recruit and retain physicians to serve the population.

Background:In individuals receiving hemodialysis, lower serum magnesium concentrations are associated with a higher risk of death and cardiovascular disease and more discomfort from muscle cramps. Small trials suggest that increasing serum magnesium by using a higher concentration of dialysate magnesium may be beneficial. This protocol outlines a large, randomized trial examining the effects of adopting a high versus low concentration of dialysate magnesium as a hemodialysis center-wide policy on the risk of mortality, major adverse cardiovascular events, and the burden of muscle cramps.Objective:To determine whether implementing a dialysate magnesium concentration of 0.75 mmol/L versus ≤ 0.5 mmol/L as a hemodialysis center-wide policy, for up to 4 years, affects (1) the rate of all-cause mortality or major cardiovascular-related hospitalizations or (2) the level of discomfort individuals experience from muscle cramps.Design:Pragmatic, 2-arm, parallel-group, registry-based, open-label, 2-sided superiority cluster randomized trial. Hemodialysis centers were randomly allocated (1:1) to one of the 2 arms. The assignment was constrained by five center-level prognostic factors and stratified by province.Setting:137 hemodialysis centers in four Canadian provinces—Ontario, British Columbia, Alberta, and Manitoba. The trial period is from April 4, 2022, to March 31, 2026. Outcomes will be analyzed after March 31, 2026, using provincial health care databases and self-reported questionnaires.Participants:Individuals who received maintenance hemodialysis at participating centers during the trial period.Intervention:Use of a dialysate magnesium concentration of either 0.75 mmol/L or ≤ 0.5 mmol/L as a center-wide policy during the trial period.Measurements:The two primary outcomes are (1) a composite of all-cause mortality or major cardiovascular-related hospitalization (a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) recorded in large health care databases and (2) self-reported muscle cramps collected from questionnaires.Methods:Using an intent-to-treat approach, the intervention effect on the instantaneous rate of the primary composite outcome will be analyzed using a stratified Cox proportional hazards model accounting for center-level clustering. The observation time will be censored for provincial emigration or the trial end date. Self-reported muscle cramps will be analyzed using a cumulative link (proportional odds) model. All models will be stratified by province and adjusted for the covariates used to constrain randomization.Limitations:The trial start date was delayed in some centers due to post-pandemic supply disruptions (including discontinued dialysate formulations); however, all centers secured dialysate concentrates in alignment with the trial-allocated magnesium level.Conclusions:The results of this pragmatic trial will inform center-wide policy on the optimal dialysate magnesium concentration for patient health.Trial Registration:www.clinicaltrials.gov; identifier: NCT04079582